Principles of pain management

Pain is an unpleasant sensation (sensory and emotional) with biological, psychological, and social components. There are several ways to classify pain, the most common being by duration (i.e., acute, subacute, and chronic). Acute pain lasts for < 1 month. It can indicate actual or potential tissue damage and is associated with trauma, surgery, and illness. Subacute pain lasts for 1–3 months, and chronic pain lasts > 3 months (i.e., beyond normal tissue healing time). Clinical evaluation of pain involves a thorough history, physical examination, and assessment of pain severity using a standardized pain intensity scale. Pain management is multimodal and can include analgesics, nonpharmacological analgesia, and interventional pain management strategies. The WHO analgesic ladder can help clinicians select an appropriate pain management strategy based on pain severity and response to existing management.

The principles of pain management are detailed in this article. Acute pain management, chronic noncancer pain management, and pain management in palliative care are detailed separately.

By duration

• Acute pain
  • A warning signal indicating actual or potential tissue damage that triggers a protective reaction
  • Typically associated with trauma, surgery, and acute illness
  • Lasts < 1 month ^[1]
• Subacute pain: lasts 1–3 months ^[1]
• Chronic pain
  • Pain that lasts beyond the normal tissue healing time (> 3 months) ^[1][2]
  • Unlike acute pain, chronic pain has no protective role in preventing further tissue damage and can be considered a disease entity in its own right.

By type

• Nociceptive pain: pain that is triggered by chemical, mechanical, or thermal stimuli (noxious stimuli)
  • Somatic pain (musculoskeletal pain): localized, sharp pain that varies in duration and quality (Aδ fibers)
  • Visceral pain: dull, diffuse, deep pain (C fibers)
• Neuropathic pain: pain caused by abnormal neural activity that arises secondary to injury, disease, or dysfunction of the nervous system
  • Central pain: caused by CNS dysfunction (e.g., poststroke pain syndrome, phantom limb pain syndrome)
  • Peripheral pain: caused by damage to peripheral nerves; (e.g., diabetic neuropathy, postherpetic neuralgia)
  • Sympathetically mediated pain: caused by damage to autonomic nerves (e.g., complex regional pain syndrome)
• For an overview of pain symptoms in patients with serious or life-threatening illnesses, see “Pain concepts in palliative care.”

Pain pathway

Nociceptors detect a chemical, mechanical, or thermal noxious stimulus → conversion of stimulus to an electric signal (action potential) ; → C fibers and Aδ fibers carry afferent input to the dorsal horn of the spinal cord → secondary nociceptive neurons in the spinothalamic tract carry afferent input to the thalamus in the CNS → pain perception and a response sent along efferent pathways, which results in pain modulation and/or a reaction ^[3]

Withdrawal reflex

A polysynaptic spinal reflex that causes a part of the body to move away from a painful stimulus (e.g., a hot object) via contraction of flexor muscles and relaxation of extensor muscles ^[3]

Pain sensitization ^[4][5]

• Abnormal pain perception due to increased neuronal sensitivity to noxious stimuli (hyperalgesia) and/or reduced neuronal threshold to otherwise normal stimuli (allodynia) in response to local injury, inflammation, and/or repetitive stimulation
• Plays a major role in the generation and maintenance of chronic pain and neuropathic pain (e.g., postherpetic neuralgia)
• Although not completely understood, the pathophysiology is thought to involve the following two mechanisms:
  • Peripheral sensitization
    • Injury, inflammation, or repetitive stimulation of the peripheral nociceptive neurons → local release of chemical mediators (e.g., cytokines, nerve growth factors, histamine)→ repeated or prolonged exposure to chemical mediators upregulates the ion channels in the nociceptors → increases sensitivity and/or reduces threshold to chemical mediators even further → increased action potentials → abnormal pain perception
    • Usually ceases once the tissue injury or inflammation heals
  • Central sensitization
    • Injury and/or inflammation of the CNS (e.g., dorsal horn of the spinal cord, brain) → increased excitability and reduced inhibition in the CNS and recruitment of non-nociceptive fibers (e.g., Aβ fibers) into the nociceptive pathway → abnormal pain perception
    • Chronic peripheral pain disorders can be a significant driver to the sensitization of central nociceptive neurons
    • Usually continues even after the initial injury has healed

Referred pain

• Definition: pain that is perceived at a location other than that of the causative stimulus; projection of pain usually onto a specific dermatome or myotome of the corresponding segment of the spinal cord
• Common examples of referred pain
  • Right shoulder pain in patients with cholecystitis or perforated PUD
  • Kehr sign: left shoulder pain associated with diaphragmatic irritation resulting from hemoperitoneum (classically secondary to splenic rupture)
  • Left-sided chest and arm pain: myocardial infarction
  • Periumbilical pain in the early stages of appendicitis
• Treatment: Select treatments may reverse this pathway.

References:^[6][7]

Phantom limb syndrome

• Definition
  • Phantom sensation: is a sensation that the amputated limb is still partially or totally existent
  • Phantom pain: sensation of pain in an amputated limb
    • Intermittent pain of varying character (e.g., burning, tingling, shooting, itching, squeezing, aching, electric shock-like sensation)
    • Onset usually within days to weeks after amputation; pain often resolves or lessens over time
• Incidence: common complication after upper or lower extremity amputation
• Pathophysiology: primary somatosensory cortex neurons that formerly respond to signals from the amputated limb respond to signals from adjacent neurons that carry sensation from other parts of the body → functional reorganization of the somatosensory cortex ^[8]
• Diagnosis: diagnosed only after exclusion of other causes of stump pain (e.g., infection, ischemia, post-surgical neuroma)
• Treatment: multimodal approach
  • Mirror therapy: Using a mirror, the existing limb is reflected in a way that makes it appear in the place of the amputated limb. The patient learns to reposition the missing limb using visualization techniques.
  • Transcutaneous electrical nerve stimulation: an analgesic therapy used to modify pain perception by administering continuous electrical impulses via electrodes on the skin
  • NMDA receptor antagonists
  • Adjuvant therapy (e.g., tricyclic antidepressants, anticonvulsants)
• Prophylaxis: perioperative regional anesthesia

References:^[9]

To optimize pain management, a thorough history and assessment of pain is required prior to initiating treatment.

• Pain characteristics (location, quality, temporal aspects, triggers)
• Associated symptoms (changes in mobility and strength)
• Previous pain assessments and/or treatment
• Pain intensity scale: subjective grading of pain severity by the patient
  • Numeric rating scale (NRS): most common pain scale, evaluates pain on a scale from 0–10
  • Visual analog scale (VAS): visual equivalents suitable for children
  • Verbal descriptor scale
• Impact of pain
  • E.g., on daily life, sleep, activities
  • This may also be evaluated through the use of validated scales, e.g., the PEG pain scale for chronic pain
• Pain diary: regular documentation of the pain intensity to identify peaks and triggers; enables treatment optimization

Pain can be difficult to assess in nonverbal patients; obtain supporting information from caretakers and use a specialized pain score, e.g., the nonverbal pain scale.

Be aware of implicit bias in the assessment of pain: Hispanic and Black patients are less likely to receive any and/or appropriate analgesia compared to White patients, even when reported pain scores are identical. ^[10][11]

Pain is subjective! Pain scales are used to assess a patient's pain and response to pain management over time. They cannot be used to compare pain intensity between patients.

References:^[12]

WHO analgesic ladder

The WHO analgesic ladder is a 3-step algorithm for the management of acute and chronic pain.

• Regular analgesic (modified-release drugs, administered at fixed times and doses)
  • By the mouth: preferably, analgesics should be given orally.
  • By the clock: regular administration at fixed times, rather than on demand
  • By the ladder (symptom-oriented): if the patient is still in pain, it is necessary to go up a step
• Appropriate PRN medication
  • Short-acting analgesics for peaks in pain
  • If PRN medication is required ≥ 3×/day → inadequate analgesia likely; review the regular medication
• Additionally, concurrent treatment with adjuvant drugs

Nonopioid analgesics are first-line agents for pain; prescribe them alone for mild to moderate pain and in combination with opioids for severe pain. ^[14]

For both opioid and nonopioid analgesics, use the minimal effective dose for the shortest duration of time to minimize adverse effects. Pain intensity scales should be used in regular intervals to assess the success of pain management.

Oral analgesics

The following information pertains to adults. See “Pain management in children” for pediatric recommendations.

All patients being discharged with opioid medications should receive counseling on the use of prescription opioids.

Parenteral analgesics

Analgesic suppositories

• Acetaminophen
• Indomethacin
• Aspirin

Topical analgesics

Adjuvant analgesics

Anticonvulsants

Anticonvulsants are useful adjuncts in the management of neuropathic pain. They typically will not be helpful for acute pain, rather are more commonly used for chronic neuropathic pain.

• Gabapentin
• Pregabalin
• Carbamazepine

Muscle relaxants

Consider muscle relaxants in patients with pain associated with muscle spasticity.

• Cyclobenzaprine
• Methocarbamol
• Baclofen

Antidepressants

Tricyclic antidepressants and SNRIs can be helpful for chronic pain syndromes and neuropathic pain. Antidepressants for chronic or neuropathic pain are recommended by the American Society of Anesthesiologists in their 2010 guideline, but only duloxetine is FDA-approved for this indication. All others are off-label use. ^[24][25]

• Tricyclic antidepressants
  • Amitriptyline ^[26]
  • Doxepin
  • Clomipramine
• SNRIs
  • Duloxetine
  • Venlafaxine

Intravenous patient-controlled analgesia

• Infusion pump designed to release additional IV medication in response to patient's request
• Indication: severe acute pain that is difficult to manage and is expected to be limited in duration

Management of side effects of analgesics

• Laxatives (see constipation)
• Antiemetics
• Proton-pump inhibitors (PPIs): Consider in patients taking frequent NSAIDs.

Multiple nonpharmacological therapies are often used in combination (e.g., exercise therapy and cognitive behavioral therapy).

Physical modalities ^[1][27]

Consider referral to physical therapy and/or occupational therapy.

• Massage
• Thermotherapy (e.g., focused ultrasound ) ^[28]
• Desensitization techniques ^[29]
• Regular exercise (e.g. walking) and exercise therapy for chronic pain ^[1][30]

Patients may require analgesia to participate in physical therapy; maximize nonopioid pharmacological therapy first. ^[31][32]

Psychological modalities ^[1][27]

Refer to a psychologist as needed.

• Relaxation techniques ^[1]
  • Biofeedback training
  • Progressive muscle relaxation
  • Mindfulness
• Cognitive behavioral therapy
• Hypnosis ^[33][34]

Other modalities ^[1][27]

• Complementary and alternative medicine
  • Acupuncture ^[1][35]
  • Osteopathic manipulative treatment (e.g., spinal manipulation for low back pain and tension headache)
  • Mind-body techniques (e.g., yoga, tai chi)
• Interventional pain management ^[1][27]
  • For subacute or chronic pain, typically in conjunction with other pain management strategies
  • Examples include
    • Intra-articular glucocorticoid injection
    • Epidural steroid injections
    • Neuromodulation and nerve ablation techniques

Pain management in children ^[36][37]

Outpatient pain management

• Treatment is multimodal and based on severity and patient response.
• Nonopioid oral analgesia in children: preferred for mild to moderate pain
  • Acetaminophen ^[37][38][39]
  • NSAIDs (e.g., ibuprofen , naproxen) ^[37][38][39]
• Opioids: reserved for moderate to severe pain refractory to other modalities
  • Avoid opioid monotherapy.
  • Short-term courses (< 5 days) of immediate-release opioids are preferred. ^[36][40]
  • Avoid codeine and tramadol in children who are:
    • < 12 years of age
    • 12–18 years of age with risk factors for hypoventilation
  • Address safety: Provide naloxone and counseling (e.g., on opioid overdose, storage, and disposal). ^[36]
• Additional treatment modalities include:
  • Nonpharmacological analgesia
  • Topical analgesics (e.g., lidocaine )
• Children with chronic or acute-on-chronic pain (e.g., due to sickle cell disease or cancer): Coordinate with their treating specialist and consider consulting a pain specialist.

Aspirin is not recommended in most pediatric patients due to the risk of Reye syndrome. ^[38]

Procedural pain in neonates and infants

• Definition: pain and stress that occur as a result of medical procedures, e.g., IV cannulation, venipuncture, finger prick, heel lance, lumbar puncture, bone marrow aspiration
• Pathophysiology: Newborn and preterm infants are sensitive to pain and stress. ^[41]
  • Pain pathways are developed by the 20^th week of gestation.
  • Nociceptive stimuli induce behavioral, autonomic, and hormonal responses in infants similar to those seen in older individuals.
  • Chronic or recurrent exposure to nociceptive stimuli can result in sensitization of the maturing neuronal pathways → hypersensitivity to pain
• Painful procedures: common in pediatric ICU patients, preterm neonates, and children with malignancy
  • IV cannulation
  • Blood draws: venipuncture, finger prick, heel lance
  • Lumbar puncture
  • Circumcision ^[42][43]
  • Bone marrow aspiration
• Clinical indicators of pain
  • Facial grimacing
  • Crying
  • Changes in crying pattern
  • Inconsolableness
  • Irritability
  • Changes in sleep pattern
• Neonatal pain assessment
  • Scoring systems for acute and postoperative pain in infants evaluate physiological parameters , behavioral changes , and/or contextual factors.
  • Examples: premature infant pain profile (PIPP), neonatal infant pain scale (NIPS), neonatal pain agitation sedation scale (N-PASS), crying, requires oxygen saturation, increased vital signs, expression, sleeplessness (CRIES) score
• Management ^[41][44]
  • General principles
    • Appropriate analgesia according to the stages of the WHO analgesic ladder
    • Preemptive analgesia for painful procedures administered before, during, and after the procedure
    • Regular assessment of the severity of pain and response to analgesia
    • The choice of the step depends on the anticipated intensity of pain
    • Steps can be combined if single measures are insufficient.
  • Analgesic steps (neonatal pain ladder)
    • Step 1: nonpharmacological measures, e.g., breastfeeding, use of a pacifier, skin-to-skin contact, oral sucrose
    • Step 2: topical analgesia (e.g., topical lidocaine, tetracaine gel)
    • Step 3: oral, rectal, or IV administration of acetaminophen or NSAIDs
    • Step 4: IV infusion of opioids
    • Step 5: subcutaneous infiltration of lidocaine or specific nerve blocks
    • Step 6: sedation or general anesthesia

• One-Minute Telegram 61-2022-2/3: Pain control after arthroscopy: Just say no to (more) narcotics!

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